ArticleNature communications2016
The HMGB1 protein induces a metabolic type of tumour cell death by blocking aerobic respiration.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- HMGB1: an overview of its versatile roles in the pathogenesis of colorectal cancer.Cellular oncology (Dordrecht, Netherlands) · 2020Pooled it
- HMGB3 facilitates malignant phenotype of esophageal carcinoma via histone lactylation- and Wnt/β-catenin-dependent transcription activation of c-myc.NPJ precision oncology · 2026Article
- DAMP signaling networks: from receptors to diverse pathophysiological functions.Journal of advanced research · 2026Review
- Review
- Necrotic Bone Fluid Suppresses Energy Metabolism of Porcine PBMC-Derived Macrophages In Vitro.Cells · 2025Article
- Oncolytic Viruses as a Novel Therapeutic Approach for Colorectal Cancer: Mechanisms, Current Advances, and Future Directions.Cancers · 2025Review
- High-Resolution Molecular-Dynamics Simulations of the Pyruvate Kinase Muscle Isoform 1 and 2 (PKM1/2).Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Significance of Malic Enzyme 1 in Cancer: A Review.Current issues in molecular biology · 2025Review
- Energy Metabolism and Stemness and the Role of Lauric Acid in Reversing 5-Fluorouracil Resistance in Colorectal Cancer Cells.International journal of molecular sciences · 2025Article
- Metabolic Targets in CRC: The Emerging Role of Cytochrome P450 Inhibitors.Current pharmaceutical design · 2025Review
- Review
- Malic enzymes in cancer: Regulatory mechanisms, functions, and therapeutic implications.Redox biology · 2024Review
- Review
- A combination of a TLR7/8 agonist and an epigenetic inhibitor suppresses triple-negative breast cancer through triggering anti-tumor immune.Journal of nanobiotechnology · 2024Article
- Acute ischemia induces spatially and transcriptionally distinct microglial subclusters.Genome medicine · 2023Article
- The multifunctional protein HMGB1: 50 years of discovery.Nature reviews. Immunology · 2023Review
- Review
- Metabolic reprogramming in colorectal cancer: regulatory networks and therapy.Cell & bioscience · 2023Review
- Acetylation of NarL K188 and K192 is involved in regulating Escherichia coli anaerobic nitrate respiration.Applied microbiology and biotechnology · 2022Article
- Posttranslational S-nitrosylation modification regulates HMGB1 secretion and promotes its proinflammatory and neurodegenerative effects.Cell reports · 2022Article
Corrections and comments
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Authors and funding
23 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The high-mobility group box 1 (HMGB1) protein has a central role in immunological antitumour defense. Here we show that natural killer cell-derived HMGB1 directly eliminates cancer cells by triggering metabolic cell death. HMGB1 allosterically inhibits the tetrameric pyruvate kinase isoform M2, thus blocking glucose-driven aerobic respiration. This results in a rapid metabolic shift forcing cells to rely solely on glycolysis for the maintenance of energy production. Cancer cells can acquire resistance to HMGB1 by increasing glycolysis using the dimeric form of PKM2, and employing glutaminolysis. Consistently, we observe an increase in the expression of a key enzyme of glutaminolysis, malic enzyme 1, in advanced colon cancer. Moreover, pharmaceutical inhibition of glutaminolysis sensitizes tumour cells to HMGB1 providing a basis for a therapeutic strategy for treating cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.